Abstract 3389: A multi-gene prostate cancer liquid biopsy with > 92% accuracy in diagnosis and assessment of disease status

Published on Aug 15, 2020in Cancer Research9.727
· DOI :10.1158/1538-7445.AM2020-3389
Kambiz Rahbar22
Estimated H-index: 22
,
Mark Kidd66
Estimated H-index: 66
+ 6 AuthorsIrvin M. Modlin81
Estimated H-index: 81
(Yale University)
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Abstract
Background: There are a paucity of blood-based biomarkers with clinical utility for prostate cancer (PCa). We examined a circulating-free mRNA (27-gene) prostate cancer signature to diagnose PCa. Clinical utility of the assay was then assessed in surgical patients. Methods:Gene identification and validation: Publicly available PCa transcriptome sets (n=5) (E-GEOD-46691, E-GEOD-46602, E-GEOD-62116, E-GEOD-62667, E-GEOD-72220: n=1,159 samples); PCA cell lines (n=7) gene expression in 22Rv1 and E006AA-hT (localized); VCaP; PC-3; LNCaP; DU145 and MDA PCa2b (all metastatic) from two normal prostate epithelial lines: PWR-1E and RWPE-1 and validated in PCa tumor tissue (n=50). Transcriptome analyses: tumor compared with normal blood-based transcriptomes using gene co-expression network enrichment, differential expression and functional enrichment analyses to identify candidate markers. Blood gene expression: PCa set #I: n=132, PCA set #II: n=50 (biochemical recurrence [BCR]), BPH: n=44, controls n=55. We then constructed an artificial intelligence PCa model using classification algorithm analyses. Scoring: normalized algorithmically analyzed gene expression (0 to 100), positive score ≥20. Matched tumor/ blood samples: n=50. PSA: BPH (n=44) and PCa (n=132). Clinical score assessment: Score utility was assessed in surgical cohorts: Surgical: (n=47), scores =pre-surgical and post: 1 week - 14 months. Statistics: Non-parametric (Kruskal-Wallis), Pearson-correlation, Fisher9s and AUROC analyses (Mean±SEM). Results: Transcriptomic analysis identified a 27 gene blood signature for PCa. Expression levels were significantly elevated (p 10ng/ml in 30%. PSA was positive in 83% of PCa and >10ng/ml in 40% (Fisher9s exact: p=0.28). PSA accuracy (>10ng/ml) was 48%. Levels in PCA #II (BCR) were 44±3. ProstaTest-was positive in 48 (96%). Surgical cohort (n=47): PCa Prostatest accuracy 100% pre-surgery. Resection significantly decreased levels (KW-statistic: 57.4, p Conclusion: The diagnostic accuracy of a PCa molecular blood-signature was 92%; significantly better than PSA (48%, p Citation Format: Kambiz Rahbar, Mark Kidd, Ignat Drozdov, Alexandra Kitz, Anna Malczewska, Pawel Rajwa, Christof Bernemann, Lisa Bodei, Irvin Modlin. A multi-gene prostate cancer liquid biopsy with > 92% accuracy in diagnosis and assessment of disease status [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3389.
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